A growing body of literature indicates that exposure to childhood adversities and trauma (CATs) significantly increases the risk of lifelong physical morbidity, including: pulmonary, cardiovascular, and gastrointestinal conditions, metabolic syndrome, some cancers, Alzheimer?s disease, psychiatric disorders, and, especially, physical-psychiatric comorbidities. Moreover, CATs exposures are quite common and are therefore potentially associated with a significant proportion of adult comorbidities and mortality. Fortunately, there is emerging literature that points to reprogramming of the immune/inflammatory system as a possible link between CATs and negative physical and/or psychiatric sequelae. While the biological pathways are not yet well understood, a better characterization of these relationships could point to interventions to aid in early identification, prevention and treatment of those exposed to CATs. The necessary research has been hampered by the difficulty of finding and assessing cohorts that are sufficiently large, associated with well-defined exposures and assessed longitudinally to ascertain objective evidence of long-term sequelae. To address these challenges, this proposal draws on a longitudinal cohort, the Stress & Well-Being (S&W) Study and its follow up study, S&W2. This is the largest (N= 1,500), most comprehensive physical and mental health study of children exposed to a shared trauma, namely, 9/11. The S&W2 funding structure allowed for collecting and bio-banking of blood but necessitated a separate proposal for its analysis, thus making the proposed Childhood Mass Trauma Exposure, Inflammatory Programming, and Psychopathology in Young Adulthood (also called Inflammation and Childhood Adversity and Trauma [I-CATs]) Study very cost-effective. Drawing on data from the two waves of S&W and S&W2, notably bio-banked blood from S&W2, this proposal is designed to characterize the relationship between exposure to CATs and subsequent profiles of inflammatory/immune signatures, and the relationship of those signatures to long-term comorbidities. Our diverse immune profiling panel includes 60 cytokines, chemokines and growth factors selected as being broadly representative of the proinflammatory, anti-inflammatory/counter-regulatory, Th17 and T regulatory (Treg) arms of the immune system, as well as neuroimmune molecules, such as BDNF and ?NGF. In summary, the I-CATs Study will: 1) identify the relationship of a shared mass trauma exposure to inflammatory signatures; 2) characterize the role (possibly a mediating role) that those immune/inflammatory signatures have on physical, psychiatric and comorbid outcomes in young adults; and, 3) ultimately, identify approaches from the immune/inflammatory domain to potentially bear on early prevention and treatment of those exposed to CATs.